Multi-trajectories of BMI, waist circumference, gut microbiota, and incident dyslipidemia: a 27-year prospective study

Evidence is insufficient to establish a longitudinal association between combined trajectories of body mass index (BMI) and waist circumference (WC) and dyslipidemia. This study investigated the associations between multi-trajectories of BMI and WC over 24 years and the subsequent risk of dyslipidemia in a large cohort of 10,678 Chinese adults from the China Health and Nutrition Survey. Utilizing a group-based trajectory model, we identified four distinct trajectories: normal, normal-increasing, overweight-increasing, and obesity-increasing. Our results indicated that ascending trajectories of BMI and WC are significantly associated with increased odds of dyslipidemia, particularly in males, with odds ratios (OR) of 2.10, 2.69, and 3.56 for the normal-increasing, overweight-increasing, and obesity-increasing groups, respectively. Among females, the normal-increasing group exhibited a significant increased risk (OR: 1.54). Furthermore, we explored the gut microbiota associated with these trajectories, identifying 3, 8, and 4 bacterial genera linked to increasing BMI and WC in males, alongside two genera in females with the normal-increasing trajectory. We identified a total of 23, 25, and 10 differential metabolites significantly associated with these genera, except for Group 2 in males. The inclusion of relevant microbiome and metabolite data improved the model's predictive capacity for the risk of dyslipidemia, with ROC values increasing from 0.655 to 0.875. Our findings underscore the critical implications of continuous weight gain on metabolic health and suggest that gut microbiota may play a pivotal role in understanding these associations.IMPORTANCEEmerging evidence suggests a close connection between the gut microbiome and both human obesity and dyslipidemia, suggesting that the gut microbiome may play an important role in the obesity-dyslipidemia relationship. In this study, we observed several characteristic genera, including <i>Clostridium_sensu_stricto_1</i>, <i>Turicibacter</i>, and CHKCI002 among males and <i>Parabacteroides</i> and <i>[Eubacterium]_brachy_group</i> among females, which were negatively associated with high-risk trajectories. They were also related to free fatty acids (FFAs) and oxidized lipid metabolites. These shared and unique gut microbial and metabolic signatures among combined trajectories of BMI and WC with a higher risk of dyslipidemia could provide important evidence for the omics mechanism pathway of long-term obesity trend leading to dyslipidemia.